Review article
Body fluid abnormalities in severe hyperglycemia in patients on chronic dialysis: review of published reports

https://doi.org/10.1016/j.jdiacomp.2007.06.012Get rights and content

Abstract

Reports of dialysis-associated hyperglycemia (DH) were compared to reports of diabetic ketoacidosis (DKA) and nonketotic hyperglycemia (NKH) in patients with preserved renal function. Average serum values in DH (491 observations), DKA (1036 observations), and NKH (403 observations) were as follows, respectively: glucose, 772, 649, and 961 mg/dl; sodium, 127, 134, and 149, mmol/l; and tonicity, 298, 304, and 355 mOsm/kg. Assuming that euglycemic (serum glucose, 90 mg/dl) values were the same (sodium, 140 mmol/l; tonicity, 285 mOsm/kg) for all three states, the hyperglycemic rise in the average serum tonicity value per 100-mg/dl rise in serum glucose concentration was 1.9 mOsm/kg in DH, 3.5 mOsm/kg in DKA, and 8.1 mOsm/kg in NKH. Neurological manifestations in DH patients were caused by coexisting conditions (ketoacidosis, sepsis, and neurological disease) in most instances, and by severe hypertonicity (>320 mOsm/kg), with clearing after insulin administration, in a few instances. In 148 episodes of DH corrected with insulin only, the mean increase in serum sodium per 100-mg/dl decrease in serum glucose (Δ[Na]/Δ[Glu]) was −1.61 mmol/l. In agreement with theoretical predictions, Δ[Na]/Δ[Glu] was numerically smaller in patients with edema than in those with euvolemia. The average hyperglycemic increase in extracellular volume, calculated from changes in serum sodium concentration during correction of DH using insulin alone, was 0.013 l/l per 100-mg/dl increase in serum glucose concentration. A small number of DH patients presented with pulmonary edema rectified by insulin alone. DH causes modest hypertonicity, with few patients having neurological manifestations caused usually by other coexisting conditions. In contrast to DKA or NKH, which usually presents with hypovolemia, DH causes hypervolemia manifested occasionally by pulmonary edema. Insulin is adequate treatment for DH.

Introduction

Dialysis-associated hyperglycemia (DH) causes potentially different solute and fluid disturbances from hyperglycemia developing in patients with preserved renal function because it is not complicated by large osmotic diuresis. Hyperglycemia should cause hypertonic states in both patients on dialysis and those with preserved renal function. However, unlike severe hyperglycemia in preserved renal function, which routinely causes clinically significant extracellular (EC) volume deficits, DH causes EC expansion. The baseline status of EC volume is theoretically a major determinant of the degree of both hypertonicity and EC volume expansion in DH, with edematous patients predicted to have greater hypertonicity and greater EC hypervolemia than euvolemic or hypovolemic subjects with the same degree of hyperglycemia (Tzamaloukas et al., in press).

In this report, we analyzed published reports on DH. We addressed three questions: (a) Do laboratory findings conform with theoretical predictions of solute and fluid abnormalities in DH? (b) Are specific predictions of the magnitude of body solute and fluid abnormalities in DH translated into clinical manifestations? (c) Do abnormalities in tonicity and EC volume differ between DH and hyperglycemia developing in patients with intact renal function?

The level of evidence of reports on severe hyperglycemia tends to be low because such reports are routinely retrospective and observational. With this proviso in mind, we analyzed published reports of severe DH and compared their findings on disturbances in body solute and fluids to those of major published studies in patients with preserved renal function and either diabetic ketoacidosis (DKA) or nonketotic hyperglycemia (NKH). Based on this analysis, we developed a treatment plan for DH.

Section snippets

Tonicity and related clinical manifestations upon presentation with hyperglycemia

Osmolality and tonicity are related but not synonymous. Serum osmolality is determined by the sum of all solutes in the serum, while tonicity, or effective osmolality, is the part of total osmolality contributed by EC solutes having difficulty crossing cell membranes and therefore causing (when their EC concentration changes) steady-state fluid shifts between the EC compartment and the intracellular (IC) compartment. A high urea concentration is routinely encountered in DH (Tzamaloukas et al.,

EC volume in DH

Table 5 shows fractional increases in EC volume at the peak of hyperglycemia {(ΔV/V1)/Δ[Glu]} calculated from the change in serum sodium concentration during the correction of hyperglycemia with insulin infusion only in the studies shown in Table 4. There is consistency between the different studies. In a hypothetical euvolemic patient with 14 l of euglycemic EC volume who develops a 66.7-mmol/l (1200 mg/dl) increase in serum glucose concentration, the calculated increase in EC volume using the

Acknowledgment

This work was supported by the New Mexico VA Health Care System.

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